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Inflammatory Bowel Diseases Are Associated With an Increased Risk for Chronic Kidney Disease, Which Decreases With Age

  • Ravy K. Vajravelu
    Correspondence
    Reprint requests Address requests for reprints to: Ravy K. Vajravelu, MD, MSCE, University of Pennsylvania, Division of Gastroenterology, 3400 Civic Center Boulevard, Perelman Center for Advanced Medicine – South Pavilion 7th Floor, Philadelphia, Pennsylvania 19104-6021. fax: (215) 349-5915.
    Affiliations
    Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Lawrence Copelovitch
    Affiliations
    Division of Nephrology, Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Mark T. Osterman
    Affiliations
    Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Frank I. Scott
    Affiliations
    Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Division of Gastroenterology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado
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  • Ronac Mamtani
    Affiliations
    Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • James D. Lewis
    Affiliations
    Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Michelle R. Denburg
    Affiliations
    Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Division of Nephrology, Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Published:November 01, 2019DOI:https://doi.org/10.1016/j.cgh.2019.10.043

      Background & Aims

      It is not clear what factors affect risk of chronic kidney disease (CKD) in patients with inflammatory bowel disease (IBD); increased risk has been inconsistently associated with use of 5-aminosalicylates (5-ASAs). We aimed to calculate the relative hazard of CKD among patients with IBD, adjusted for CKD risk factors, and to determine whether IBD medications are associated with change in estimated glomerular filtration rate (eGFR).

      Methods

      We performed a retrospective cohort study of data from The Health Improvement Network. Patients with IBD (n = 17,807) were matched for age, sex, and practice to individuals without IBD (n = 63,466). The relative hazard of CKD, stages 3 through 5D, in patients with IBD was calculated using a Cox proportional hazards model adjusted for common CKD risk factors. We also evaluated the association of 5-ASAs, azathioprine, and methotrexate with change in eGFR using a longitudinal model.

      Results

      After we controlled for risk factors associated with CKD, we found IBD to be associated with development of CKD in patients 16–77 years old. As patient age increased, the adjusted hazard ratio for CKD decreased monotonically, from 7.88 (95% CI, 2.56–24.19) at age 16 to 1.13 (95% CI, 1.01–1.25) at age 77. In the longitudinal analysis, exposure to 5-ASAs or methotrexate was not associated with change in eGFR, whereas azathioprine was associated with a slightly higher eGFR (0.32 mL/min/1.73 m2; 95% CI, 0.16–0.48).

      Conclusions

      In a retrospective study of more than 80,000 persons, we found that IBD is associated with increased risk of CKD, and the hazard ratio is highest among younger patients. Commonly used non-biologic therapeutic agents were not associated with lower eGFR.

      Keywords

      Abbreviations used in this paper:

      aHR (adjusted hazard ratio), CI (confidence interval), CKD (chronic kidney disease stages 3–5), eGFR (estimated glomerular filtration rate), IBD (inflammatory bowel disease), IQR (interquartile range), IR (incidence rate), THIN (The Health Improvement Network)
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      References

        • Peyrin-Biroulet L.
        • Loftus Jr., E.V.
        • Colombel J.F.
        • et al.
        Long-term complications, extraintestinal manifestations, and mortality in adult Crohn's disease in population-based cohorts.
        Inflamm Bowel Dis. 2011; 17: 471-478
        • Van Staa T.P.
        • Travis S.
        • Leufkens H.G.M.
        • et al.
        5-aminosalicylic acids and the risk of renal disease: a large British epidemiologic study.
        Gastroenterology. 2004; 126: 1733-1739
        • Lewis B.
        • Mukewar S.
        • Lopez R.
        • et al.
        Frequency and risk factors of renal insufficiency in inflammatory bowel disease inpatients.
        Inflamm Bowel Dis. 2013; 19: 1846-1851
        • Primas C.
        • Novacek G.
        • Schweiger K.
        • et al.
        Renal insufficiency in IBD: prevalence and possible pathogenetic aspects.
        J Crohns Colitis. 2013; 7: e630-e634
        • Bernstein C.N.
        • Wajda A.
        • Blanchard J.F.
        The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study.
        Gastroenterology. 2005; 129: 827-836
        • Park S.
        • Chun J.
        • Han K.D.
        • et al.
        Increased end-stage renal disease risk in patients with inflammatory bowel disease: a nationwide population-based study.
        World J Gastroenterol. 2018; 24: 4798-4808
        • Novis B.H.
        • Korzets Z.
        • Chen P.
        • et al.
        Nephrotic syndrome after treatment with 5-aminosalicylic acid.
        Br Med J (Clin Res Ed). 1988; 296: 1442
        • Barbour V.M.
        • Williams P.F.
        Nephrotic syndrome associated with sulphasalazine.
        BMJ. 1990; 301: 818
        • Dwarakanath A.D.
        • Michael J.
        • Allan R.N.
        Sulphasalazine induced renal failure.
        Gut. 1992; 33: 1006-1007
        • Fornaciari G.
        • Maccari S.
        • Borgatti P.P.
        • et al.
        Nephrotic syndrome from 5-ASA for ulcerative colitis? Complicated by carcinoma of the colon and sclerosing cholangitis.
        J Clin Gastroenterol. 1997; 24: 37-39
        • Schreiber S.
        • Hamling J.
        • Zehnter E.
        • et al.
        Renal tubular dysfunction in patients with inflammatory bowel disease treated with aminosalicylate.
        Gut. 1997; 40: 761-766
        • Thuluvath P.J.
        • Ninkovic M.
        • Calam J.
        • et al.
        Mesalazine induced interstitial nephritis.
        Gut. 1994; 35: 1493-1496
        • Witte T.
        • Olbricht C.J.
        • Koch K.M.
        Interstitial nephritis associated with 5-aminosalicylic acid.
        Nephron. 1994; 67: 481-482
        • Mahmud N.
        • McDonald G.S.
        • Kelleher D.
        • et al.
        Microalbuminuria correlates with intestinal histopathological grading in patients with inflammatory bowel disease.
        Gut. 1996; 38: 99-103
        • Kreisel W.
        • Wolf L.M.
        • Grotz W.
        • et al.
        Renal tubular damage: an extraintestinal manifestation of chronic inflammatory bowel disease.
        Eur J Gastroenterol Hepatol. 1996; 8: 461-468
        • Ambruzs J.M.
        • Walker P.D.
        • Larsen C.P.
        The histopathologic spectrum of kidney biopsies in patients with inflammatory bowel disease.
        Clin J Am Soc Nephrol. 2014; 9: 265-270
        • Greenstein A.J.
        • Sachar D.B.
        • Panday A.K.
        • et al.
        Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients.
        Medicine (Baltimore). 1992; 71: 261-270
        • Parks J.H.
        • Worcester E.M.
        • O'Connor R.C.
        • et al.
        Urine stone risk factors in nephrolithiasis patients with and without bowel disease.
        Kidney Int. 2003; 63: 255-265
        • Cury D.B.
        • Moss A.C.
        • Schor N.
        Nephrolithiasis in patients with inflammatory bowel disease in the community.
        Int J Nephrol Renovasc Dis. 2013; 6: 139-142
        • Alexander R.T.
        • Hemmelgarn B.R.
        • Wiebe N.
        • et al.
        Kidney stones and kidney function loss: a cohort study.
        BMJ. 2012; 345: e5287
        • Denburg M.R.
        • Jemielita T.O.
        • Tasian G.E.
        • et al.
        Assessing the risk of incident hypertension and chronic kidney disease after exposure to shock wave lithotripsy and ureteroscopy.
        Kidney Int. 2016; 89: 185-192
        • Denburg M.R.
        • Haynes K.
        • Shults J.
        • et al.
        Validation of The Health Improvement Network (THIN) database for epidemiologic studies of chronic kidney disease.
        Pharmacoepidemiol Drug Saf. 2011; 20: 1138-1149
        • Smith D.H.
        • Shetterly S.
        • Flory J.
        • et al.
        Diagnosis-based cohort augmentation using laboratory results data: the case of chronic kidney disease.
        Pharmacoepidemiol Drug Saf. 2018; 27: 872-877
        • Chan M.R.
        • Dall A.T.
        • Fletcher K.E.
        • et al.
        Outcomes in patients with chronic kidney disease referred late to nephrologists: a meta-analysis.
        Am J Med. 2007; 120: 1063-1070
        • Lewis J.D.
        • Bilker W.B.
        • Weinstein R.B.
        • et al.
        The relationship between time since registration and measured incidence rates in the General Practice Research Database.
        Pharmacoepidemiol Drug Saf. 2005; 14: 443-451
        • Lewis J.D.
        • Brensinger C.
        • Bilker W.B.
        • et al.
        Validity and completeness of the General Practice Research Database for studies of inflammatory bowel disease.
        Pharmacoepidemiol Drug Saf. 2002; 11: 211-218
        • Pigneur B.
        • Escher J.
        • Elawad M.
        • et al.
        Phenotypic characterization of very early-onset IBD due to mutations in the IL10, IL10 receptor alpha or beta gene: a survey of the Genius Working Group.
        Inflamm Bowel Dis. 2013; 19: 2820-2828
        • Atiyeh B.A.
        • Dabbagh S.S.
        • Gruskin A.B.
        Evaluation of renal function during childhood.
        Pediatr Rev. 1996; 17: 175-180
        • Heilbron D.C.
        • Holliday M.A.
        • al-Dahwi A.
        • et al.
        Expressing glomerular filtration rate in children.
        Pediatr Nephrol. 1991; 5: 5-11
        • Schwartz G.J.
        • Munoz A.
        • Schneider M.F.
        • et al.
        New equations to estimate GFR in children with CKD.
        J Am Soc Nephrol. 2009; 20: 629-637
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • Lewis J.D.
        • Aberra F.N.
        • Lichtenstein G.R.
        • et al.
        Seasonal variation in flares of inflammatory bowel disease.
        Gastroenterology. 2004; 126: 665-673
        • Grainge M.J.
        • West J.
        • Card T.R.
        Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study.
        Lancet. 2010; 375: 657-663
        • Zallot C.
        • Billioud V.
        • Frimat L.
        • et al.
        5-Aminosalicylates and renal function monitoring in inflammatory bowel disease: a nationwide survey.
        J Crohns Colitis. 2013; 7: 551-555
        • Vadasz Z.
        • Haj T.
        • Kessel A.
        • et al.
        Age-related autoimmunity.
        BMC Med. 2013; 11: 94
        • Herzog D.
        • Fournier N.
        • Buehr P.
        • et al.
        Age at disease onset of inflammatory bowel disease is associated with later extraintestinal manifestations and complications.
        Eur J Gastroenterol Hepatol. 2018; 30: 598-607
        • Vajravelu R.K.
        • Scott F.I.
        • Mamtani R.
        • et al.
        Medication class enrichment analysis: a novel algorithm to analyze multiple pharmacologic exposures simultaneously using electronic health record data.
        J Am Med Inform Assoc. 2018; 25: 780-789
        • Ogdie A.
        • Yu Y.
        • Haynes K.
        • et al.
        Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study.
        Ann Rheum Dis. 2015; 74: 326-332
        • Vajravelu M.E.
        • Keren R.
        • Weber D.R.
        • et al.
        Incidence and risk of celiac disease after type 1 diabetes: a population-based cohort study using the health improvement network database.
        Pediatr Diabetes. 2018; 19: 1422-1428
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      Linked Article

      • Link Between Inflammatory Bowel Disease and Risk of Chronic Kidney Disease
        Clinical Gastroenterology and HepatologyVol. 19Issue 9
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          We read the article by Vajravelu et al1 with great interest. The authors conducted a crucial study to examine the link between inflammatory bowel disease (IBD) and the risk of chronic kidney disease (CKD) with excellent methodology in a large retrospective cohort from the United Kingdom electronic records database. Their study adds valuable insight for health care personnel in that CKD could be significantly induced by IBD. Although the authors acknowledged the limitations of their study, we wish to further emphasize several methodological issues and provide our careful interpretation of the data.
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